TLR7 and Immune Response Regulation

Thu, 01/10/2013 - 16:57

Toll-like receptor 7 (TLR7) is a protein encoded by the TLR7 gene in humans and is a member of TLR family. TLRs controls host immune response against pathogens (e.g. viruses, bacteria and fungi) through recognition of pathogen-associated molecular patterns (PAMPs) which are specific to the microorganisms. These pathogen-associated molecular markers are class-specific and mutation-resistant and may be composed of proteins, carbohydrates, lipids, nucleic acids and/or combinations. Recognition of PAMPs by TLRs leads to a series of signaling events resulting in the production of cytokines necessary for the development of effective immunity.

The natural ligands of TLR7 were recently identified as single-stranded RNA (ssRNA), such as ssRNA from influenza viruses (2). The interaction between viral ssRNA and TLR7 occurs in an endosomal compartment in the cell. TLR7 then signals through the cytoplasmic adaptor protein MyD88, which leads to the downstream activation of interferon response factor-7 (IRF7) and induction of Interferon (IFN)-alpha /beta gene expression. ssRNA from non-viral origin can also induce TRL7-dependent production of inflammatory cytokines.

Western Blot: TLR7 Antibody

A combination drug composed of INF-alpha and ribavirin is currently the mainstay treatment for chronic hepatitis C virus (HCV) infection although only with partial success. Recently, synthetic TLR7 agonists have been proposed as a replacement for INF-alpha to treat HCV infection and are being used clinically. However, the adverse effects (such as lymphopenia and cardiovascular irregularities) causes by the synthetic agonists were observed and thought to be too toxic for clinical use (3). Thus, many pharmaceutical companies have been focused on developing new, effective and safe TLR7 agonists.

Research also has revealed that TLR7 agonists may be a promising strategy for the immunotherapy of cancer (4). Imiquimod, a small molecule of TLR7 agonist, has been used successfully for the topical treatment of skin cancer, such as basal cell carcinoma. A systemic application of TLR7 ligands was shown to functionally activate both CD8+T cells and natural killer cells, two major effector cell types responsible for anticancer actions.

More studies on TLR7: Pancreatic carcinogenesis in mice and humans may be dependent on TLR7 signaling (5); Control of TLR7 expression showed to be essential to restrict the development of autoimmune pathologies (6); A synthetic TLR7 agonist (S-28463) prevents an allergic asthma and exhibits anti-inflammatory action (7).

  1. PMID: 15596124
  2. PMID: 14976261
  3. PMID: 22476912
  4. PMID: 22720251
  5. PMID: 23023703
  6. PMID: 17997333

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